title: A randomized trial of vitamin D₃ supplementation in children: dose-response effects on vitamin D metabolites and calcium absorption.
abstract: BACKGROUND
  Changes in serum vitamin D metabolites and calcium absorption with varying doses of oral vitamin D₃ in healthy children are unknown.
  
  
  OBJECTIVE
  Our objective was to examine the dose-response effects of supplemental vitamin D₃ on serum vitamin D metabolites and calcium absorption in children living at two U.S. latitudes.
  
  
  METHODS
  Black and white children (n = 323) participated in a multisite (U.S. latitudes 34° N and 40° N), triple-masked trial. Children were randomized to receive oral vitamin D₃ (0, 400, 1000, 2000, and 4000 IU/d) and were sampled over 12 weeks in winter. Serum 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)₂D) were measured using RIA and intact PTH (iPTH) by immunoradiometric assay. Fractional calcium absorption was determined from an oral stable isotope ⁴⁴Ca (5 mg) in a 150-mg calcium meal. Nonlinear and linear regression models were fit for vitamin D metabolites, iPTH, and calcium absorption.
  
  
  RESULTS
  The mean baseline 25(OH)D value for the entire sample was 70.0 nmol/L. Increases in 25(OH)D depended on dose with 12-week changes ranging from -10 nmol/L for placebo to 76 nmol/L for 4000 IU. Larger 25(OH)D gains were observed for whites vs blacks at the highest dose (P < .01). Gains for 1,25(OH)₂D were not significant (P = .07), and decreases in iPTH were not dose-dependent. There was no dose effect of vitamin D on fractional calcium absorption when adjusted for pill compliance, race, sex, or baseline 25(OH)D.
  
  
  CONCLUSIONS
  Large increases in serum 25(OH)D with vitamin D₃ supplementation did not increase calcium absorption in healthy children living at 2 different latitudes. Supplementation with 400 IU/d was sufficient to maintain wintertime 25(OH)D concentrations in healthy black, but not white, children.
authors.affiliation: PhD, The University of Georgia, 279 Dawson Hall, Athens, GA 30602. rlewis@uga.edu.
authors.forename: R D
authors.initials: RD
authors.lastname: Lewis
authors.forename: E M
authors.initials: EM
authors.lastname: Laing
authors.forename: K M
authors.initials: KM
authors.lastname: Hill Gallant
authors.forename: D B
authors.initials: DB
authors.lastname: Hall
authors.forename: G P
authors.initials: GP
authors.lastname: McCabe
authors.forename: D B
authors.initials: DB
authors.lastname: Hausman
authors.forename: B R
authors.initials: BR
authors.lastname: Martin
authors.forename: S J
authors.initials: SJ
authors.lastname: Warden
authors.forename: M
authors.initials: M
authors.lastname: Peacock
authors.forename: C M
authors.initials: CM
authors.lastname: Weaver
mesh_terms: D000293:Adolescent; D001741:Black or African American; D002112:Calcifediol / Q000097:blood / Q000378:metabolism; D002117:Calcitriol / Q000097:blood / Q000378:metabolism; D002136:Calcium, Dietary / Q000378:metabolism*; D002648:Child; D002657:Child Development; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D019587:Dietary Supplements / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005845:Georgia; D006801:Humans; D007196:Indiana; D007408:Intestinal Absorption / Q000208:ethnology; D008297:Male; D008954:Models, Biological; D010281:Parathyroid Hormone / Q000097:blood / Q000378:metabolism; D012621:Seasons; D013472:Sunlight; D014808:Vitamin D Deficiency / Q000097:blood / Q000208:ethnology / Q000378:metabolism / Q000517:prevention & control*; D044465:White People
chemical_list: D002136:Calcium, Dietary; C470125:PTH protein, human; D010281:Parathyroid Hormone; D002762:Cholecalciferol; D002117:Calcitriol; D002112:Calcifediol